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Občutljivost HPV- pozitivnih in HPV- negativnih humanih celičnih linij karcinoma žrela na izbrane kemoterapevtike
Volk, Lea (Author), Čemažar, Maja (Mentor) More about this mentor... This link opens in a new window

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Abstract
HPV je epitelotrofni virus, ki okuži keratinocite v žrelu. Virusni proteini vplivajo na regulacijo celičnega cikla in popravljalne sisteme celic, zaradi česar se normalne celice lahko transformirajo v rakave celice. Bolniki s HPV-pozitivnimi tumorji žrela se bolje odzivajo na zdravljenje z radiokemoterapijo kot bolniki s HPV-negativnimi tumorji žrela. Zaradi hudih neželenih učinkov zdravljenja je smiselno zmanjšanje intenzivnosti zdravljenja za bolnike s HPV-pozitivnim rakom žrela. To vključuje zmanjšanje doze obsevanja in znižanje koncentracije ali zamenjavo kemoterapevtikov z manj škodljivimi kemoterapevtiki. Ovrednotili smo odziv HPV-pozitivne (SCC090) in HPV-negativne (Detroit 562) celične linije na obsevanje in izpostavitev kemoterapevtikom cisplatinu, bleomicinu in karboplatinu. Učinek obsevanja in kemoterapevtikov cisplatina, bleomicina in karboplatina na izbrani celični liniji smo določali s testom klonogenosti in s testom metabolne aktivnosti celic. Pokazali smo, da sta HPV-pozitivna (SCC090) in HPV-negativna (Detroit 562) celična linija enako občutljivi na obsevanje in kemoterapevtike cisplatin, bleomicin ter karboplatin. Pokazali smo tudi, da sta kemoterapevtika bleomicin in karboplatin enako citotoksična za celični liniji SCC090 in Detroit 562. Izmed izbranih kemoterapevtikov je imel cisplatin značilno največji učinek na celični liniji SCC090 in Detroit 562. Za natančnejše vrednotenje celičnih linij SCC090 in Detroit 562 bi bile potrebne nadaljnje in vitro raziskave, kot je spremljanje poškodb in popravljanja DNA, ter določanje razporeditve celic v faze celičnega cikla po obsevanju ali izpostavitvi kemoterapevtikom. Primerjali bi lahko tudi učinek drugih kemoterapevtikov na celični liniji. Celični liniji bi lahko opazovali tudi in vivo, na miših.

Language:Slovenian
Keywords:ionizirajoče sevanje, kemoterapevtiki, SCC090, Detroit562, klonogenost, viabilnost
Work type:Master's thesis/paper (mb22)
Organization:BF - Biotechnical Faculty
Year:2019
Views:15
Downloads:13
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Secondary language

Language:English
Title:Sensitivity of HPV positive and HPV negative humane oropharyngeal carcinoma cell lines to chosen chemotherapeutics
Abstract:
HPV is an epitheliotropic virus that infects keratinocytes of the pharynx. Viral proteins affect the regulation of the cell cycle and cell repair systems, which can induce transformation of normal cells into cancer cells. Patients with HPV-positive pharyngeal tumors are more responsive to treatment with radiochemotherapy than patients with HPV-negative pharyngeal tumors. Due to the severe side effects of the treatment, it is reasonable to reduce the intensity of treatment for patients with HPV-positive pharyngeal cancer. This includes reducing the radiation dose and lowering the concentration of chemotherapy or replacing used cytostatics with less harmful ones. We evaluated the response of HPV-positive (SCC090) and HPV-negative (Detroit 562) cell lines to radiation and exposure to chemotherapeutics cisplatin, bleomycin, and carboplatin. We used the clonogenic and metabolic activity assay to evaluate the effect of irradiation and exposure to chemotherapeutics cisplatin, bleomycin, and carboplatin. We have shown that the HPV-positive (SCC090) and HPV-negative (Detroit 562) cell lines are essentially equally sensitive to radiation and chemotherapeutics cisplatin, bleomycin, and carboplatin. We also demonstrated that chemotherapeutics bleomycin and carboplatin have the same effect on the SCC090 and Detroit 562 cell lines. Of the selected chemotherapeutics, cisplatin had the most significant effect on cell lines SCC090 and Detroit 562. For more detailed characterisation of SCC090 and Detroit 562 cell lines, further in vitro studies are required, which include monitoring of DNA damage repair and determination of cell distribution in the cell cycle phases after irradiation or exposure to chemotherapeutics. The effects of other chemotherapeutics on cell lines could also be compared. The comparison between the cell lines could also be performed in vivo, in laboratory mice.

Keywords:ionizing radiation/chemotherapeutics/SCC090/Detroit562/clonogenicity/viability

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